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Biomedical subjects

S Neifer

Publications and source records attributed to S Neifer.

30 records · Page 2Linked to original sources

Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria.

Elevated serum or plasma concentration of immunoreactive tumor necrosis factor (TNF) is consistently detected in patients with malaria. TNF levels correlate with high parasitemia and clinical severity but not always with outcome. Since the effects of TNF may be neutralized by soluble TNF receptors, sera of 30 nonimmune patients with malaria were analyzed before and during antimalarial therapy. High concentrations of receptors R1 (55 kDa) and R2 (75 kDa) were detected immunologically in all sera of untreated patients. Levels of immunoreactive TNF correlated closely with levels of soluble TNF R1 and R2 (r = .75 and .59, respectively). In contrast, sera lacked cytotoxic activity against target cells in the TNF bioassays. Soluble TNF receptor levels remained elevated for days after treatment. These results suggest that excessive release of TNF induced by the asexual stage of malaria parasites is controlled by a subsequent shedding of soluble TNF receptors that may bind and deactivate biologically functional TNF.

Adolescent↗

Interferon-gamma treatment in mice experimentally infected with Trichinella spiralis.

Interferon-tau (IFN-tau) treatment of Trichinella spiralis-infected BALB/c mice was investigated. The therapeutic regimen consisted of daily intraperitoneal injection of 10(4) U murine IFN-tau for 7 days, starting at 2 weeks post-infection. Striated muscle samples (diaphragm, thigh) were collected at 4, 8 and 12 weeks after infection. The muscle larval burden, the degree of encystation and the digestion of T. spiralis larvae were investigated. Furthermore, immunohistochemical studies of the inflammatory cell infiltrate around encysted larvae were performed. The results demonstrated an influence of IFN-tau treatment on the CD4+ and CD8+ subset distribution during the immune response but revealed no difference in the degree of encystation or digestion of encapsulated larvae as compared with control values.

Animals↗

Interferon-gamma enhances the effect of antimalarial chemotherapy in murine Plasmodium vinckei malaria.

Most nonimmune patients with Plasmodium falciparum infection are no longer cured by such standard antimalarial drugs as chloroquine. Thus, alternative treatment regimens are necessary. A combination therapy was tested consisting of a subcurative dose of chloroquine and interferon-gamma (IFN-gamma) in BALB/c mice with lethal Plasmodium vinckei malaria. Treatment with either agent alone prolonged median survival by 1-2 days compared with placebo-treated mice. However, a combination of 80 micrograms of chloroquine given at the time of infection plus 1 x 10(4) units of IFN-gamma/day for 11 days (starting 3 days before infection) cured 83% of infected mice. Moreover, these mice showed solid immunity when challenged with the homologous strain of P. vinckei. However, when these mice were infected with the heterologous strain of Plasmodium berghei, the same degree of parasitemia developed as did in P. berghei-infected control mice. Thus, the combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria.

Animals↗

Pentoxifylline prevents murine cerebral malaria.

Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.

Animals↗

Prevention of murine cerebral malaria by a stable prostacyclin analog.

Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.

Animals↗

Characterization of erythrocytic glucose-6-phosphate dehydrogenase in a mouse strain with reduced G6PD activity.

Erythrocytic glucose-6-phosphate dehydrogenase (G6PD) of a mutant mouse strain with X-linked G6PD-deficiency was purified and compared with the wildtype G6PD by biochemical and physiological characteristics. The red cell G6PD activity of the mutant was 20% of the wildtype. The Michaelis constant (Km) of the substrate glucose-6-phosphate (G6P) was higher (90 microM) for the mutant than for the wildtype (56 microM). The isoelectric focusing with a pH range from 3 to 10 showed one more enzymatically active band for the wildtype G6PD compared to the mutant enzyme. Other enzyme characteristics, however, such as Km for nicotinamide adenine dinucleotide phosphate (NADP), utilisation of 2-deoxy-glucose-6-phosphate (2dG6P) and deamino-NADP, heat stability, pH optimum, molecular weight, and glucose metabolisation via the pentosephosphate pathway were similar in mutant and wildtype enzyme.

Animals↗

Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production.

Accumulating evidence points toward an antagonism between TH1 and TH2 focused immune responses decisive for the outcome of parasitic infections with leishmaniae. Interferon-gamma (IFN-gamma) and interleukin 4 (IL4), the principal cytokines involved in these pathways, as well as IgE and the IgG subclasses differentially modulated by these cytokines, were therefore assessed in 18 Brazilian patients with visceral leishmaniasis. The results are compared to those of a local control group. IL4 was detected in all patient sera but in only one control. Low concentrations of IFN-gamma where detectable in 50% of the Brazilian controls but in only two patients. While group medians of mitogen-induced in vitro synthesis of IL4 and IFN-gamma were similar, release of these lymphokines correlated inversely in patients (Spearman's rho = -0.84). Elevations of serum IgE complement the lymphokine data to indicate prominent TH2 type responses in clinical infections with Leishmania donovani.

Adolescent↗

[The detection of HIV antibodies in blood stains].

Blood samples were collected on cotton wool and stored at +20 degrees C. These samples were tested in an enzyme linked immunosorbent assay and the immunoblotting test. HIV-antibodies could be detected in samples stored up to four month.

Acquired Immunodeficiency Syndrome↗

Prevalence and level of antibodies to the circumsporozoite proteins of human malaria parasites, including a variant of Plasmodium vivax, in the population of two epidemiologically distinct areas in the state of Acre, Brazil.

A seroepidemiological study of the prevalence of antibodies against the repeating epitopes of circumsporozoite (CS) proteins of human malaria parasites was conducted in 2 different areas in the state of Acre, Brazil in 1987 and 1990. In 1987 antibodies against the CS protein of the VK 247 variant Plasmodium vivax as well as antibodies against the CS proteins of P. falciparum and the classic P. vivax were found at relatively high rates in the 2 areas, but significant microepidemiological differences were observed. In 1990, when large scale migration in Amazonia had ceased and control measures were applied in the study areas, the malaria endemicity decreased, as determined by the declining prevalence of anti-sporozoite antibodies against all Plasmodium species, and the small number of individuals with positive blood smears. Antibodies against sporozoites of the variant P. vivax did not cross-react with the CS proteins of the classic P. vivax, nor with antibodies against sporozoites of P. falciparum and P. malariae. Sera containing antibodies against the CS protein of P. malariae were found at a very low frequency, and only in 1987. The anti-CS protein antibody response to all Plasmodium species was age-related.

Adolescent↗

Drug susceptibility of Plasmodium falciparum in the western Amazon region, State of Acre, Brazil.

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recommended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

Animals↗

[Retrospective evaluation of western blot for detection of early HIV infections].

The purpose of HIV diagnosis is to establish safely whether there is an infection or not. The enzyme-linked immunosorbent assay (ELISA) as screening test, and the western blot assay for confirmation is the most widely used serologic test system to get this information. Diagnostic problems occur if the two tests yield different results. In our 1993 study 491 (4.4%) of 11,127 tested sera were reactive by ELISA. 39 (7.9%) of these samples could not be confirmed by western blot, giving negative or indeterminate results. In addition, 370 ELISA-negative samples were tested by HIV-1 western blot to detect the infection in the early stage. 115 (31%) of these sera showed indeterminate western blot patterns, the other samples were negative. Results of follow-up investigations of 26 (Table 1) or 11 (Table 2) persons with indefinite serodiagnosis were analysed. HIV infection was not detected in any of these cases. In the literature, persons whose sera were reactive according to ELISA and were indeterminate in western blot, had a 3-5% probability of an aisting HIV infection. In contrast, indeterminate western blot patterns in ELISA-negative sere were without significance for the prognosis as to whether a person was or was not HIV-infected.

AIDS Serodiagnosis↗